Value of various PSA parameters for diagnosing prostate cancer in men with normal digital rectal examination

OBJECTIVES: The risks of identifying prostate cancer (PCa) in patients with serum total PSA (tPSA) between 4 and 10 ng/dl are between 25 and 35%. There are no data in Brazil showing the incidence of disease when all variables for PSA assessment are considered altogether, specifically tPSA, free fraction, PSA velocity and PSA stratified by age. The objective in this work was to define the incidence of disease in a population of men with abnormal values of PSA variables and normal digital rectal examination. MATERIALS AND METHODS: Between 1998 and 2003, 273 prostate biopsies were performed by the same radiologist and analyzed by the same pathologist. All patients had a normal digital rectal examination and biopsy had been indicated due to tPSA above 4 ng/dl or free-to-total PSA ratio (F/T PSA) below 15% or PSA velocity higher than 25% per year or a PSA level regarded as high for the age range. The relationship between these parameters and the positivity for prostate caner was determined. RESULTS: Patients' mean age was 63.8 years, and PCa was identified in 135 cases (49.5%). The incidence of PCa, related to unitary variations in tPSA, ranged from the limits of 33 to 80%, respectively, in tPSA < 3 and PSA between 15.1 to 20. When the other PSA parameters were assessed (free PSA, PSA according to age, rise velocity) PCa was detected in more than 25.3% of cases. CONCLUSION: When patients with normal digital rectal examination are selected for prostate biopsy due to tPSA levels above 4 or F/T PSA ratio lower than 15% or PSA velocity higher than 25% per year or high PSA for the age range, the incidence of PCa is quite higher than that observed in a population selected exclusively with basis on total PSA value.Universidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina (EPM) Division of UrologyUNIFESP, EPM, Division of UrologySciEL

Brazilian savannah tree as bio-inspiration for hydraulic transient control in a penstock of a small hydropower plant

This study proposes an innovation, which is to use a non-circular and bio-inspired forced conduit (a new penstock with a cross section inspired by a tree trunk), to control the effects of hydraulic transients in Brazilian small hydropower plants (SHPs). The aim is to demonstrate that natural structures, adapted to periodic environmental disturbances, are better at hydraulic transient control than traditional conduits. The proposed methodology includes the following steps: (1) problem identification; (2) potential biological model identification; (3) development of alternatives; (4) implementation and testing; and (5) solution selection. This research was conducted at the São Tadeu I SHP, in the city of Santo Antônio de Leverger/MT, Brazil. The following tree biological models from the Brazilian savannah (Cerrado) were used: Handroanthus capitatus and Strychnos pseudoquina. The proposed innovation improves the conduit of the traditional circular section and the relief valve solution of the criteria studied. The reason for this improvement was the reduction of wave speed in the non-circular section (from 1126 to 583 m s−1)

A New Era in the Quest for Dark Matter

There is a growing sense of `crisis' in the dark matter community, due to the absence of evidence for the most popular candidates such as weakly interacting massive particles, axions, and sterile neutrinos, despite the enormous effort that has gone into searching for these particles. Here, we discuss what we have learned about the nature of dark matter from past experiments, and the implications for planned dark matter searches in the next decade. We argue that diversifying the experimental effort, incorporating astronomical surveys and gravitational wave observations, is our best hope to make progress on the dark matter problem.Comment: Published in Nature, online on 04 Oct 2018. 13 pages, 1 figur

The Targeting of Plasmalemmal Ceramide to Mitochondria during Apoptosis

Ceramide is a key lipid mediator of cellular processes such as differentiation, proliferation, growth arrest and apoptosis. During apoptosis, ceramide is produced within the plasma membrane. Although recent data suggest that the generation of intracellular ceramide increases mitochondrial permeability, the source of mitochondrial ceramide remains unknown. Here, we determine whether a stress-mediated plasmalemmal pool of ceramide might become available to the mitochondria of apoptotic cells. We have previously established annexin A1—a member of a family of Ca2+ and membrane-binding proteins—to be a marker of ceramide platforms. Using fluorescently tagged annexin A1, we show that, upon its generation within the plasma membrane, ceramide self-associates into platforms that subsequently invaginate and fuse with mitochondria. An accumulation of ceramide within the mitochondria of apoptotic cells was also confirmed using a ceramide-specific antibody. Electron microscopic tomography confirmed that upon the formation of ceramide platforms, the invaginated regions of the plasma membrane extend deep into the cytoplasm forming direct physical contacts with mitochondrial outer membranes. Ceramide might thus be directly transferred from the plasma membrane to the mitochondrial outer membrane. It is conceivable that this “kiss-of-death” increases the permeability of the mitochondrial outer membrane thereby triggering apoptosis

Global disparities in SARS-CoV-2 genomic surveillance

Genomic sequencing is essential to track the evolution and spread of SARS-CoV-2, optimize molecular tests, treatments, vaccines, and guide public health responses. To investigate the global SARS-CoV-2 genomic surveillance, we used sequences shared via GISAID to estimate the impact of sequencing intensity and turnaround times on variant detection in 189 countries. In the first two years of the pandemic, 78% of high-income countries sequenced >0.5% of their COVID-19 cases, while 42% of low- and middle-income countries reached that mark. Around 25% of the genomes from high income countries were submitted within 21 days, a pattern observed in 5% of the genomes from low- and middle-income countries. We found that sequencing around 0.5% of the cases, with a turnaround time <21 days, could provide a benchmark for SARS-CoV-2 genomic surveillance. Socioeconomic inequalities undermine the global pandemic preparedness, and efforts must be made to support low- and middle-income countries improve their local sequencing capacity

Global disparities in SARS-CoV-2 genomic surveillance

Genomic sequencing is essential to track the evolution and spread of SARS-CoV-2, optimize molecular tests, treatments, vaccines, and guide public health responses. To investigate the global SARS-CoV-2 genomic surveillance, we used sequences shared via GISAID to estimate the impact of sequencing intensity and turnaround times on variant detection in 189 countries. In the first two years of the pandemic, 78% of high-income countries sequenced >0.5% of their COVID-19 cases, while 42% of low- and middle-income countries reached that mark. Around 25% of the genomes from high income countries were submitted within 21 days, a pattern observed in 5% of the genomes from low- and middle-income countries. We found that sequencing around 0.5% of the cases, with a turnaround time <21 days, could provide a benchmark for SARS-CoV-2 genomic surveillance. Socioeconomic inequalities undermine the global pandemic preparedness, and efforts must be made to support low- and middle-income countries improve their local sequencing capacity